686 



SCIENCE. 



[N. S. Vol. XX. No. 516. 



of applying the solution to the nerve-cord 

 left in connection with the muscle. It is, 

 therefore, probable that the solutions worked 

 with act on the ganglion cells directly rather 

 than indirectly by stimulation of sensory 

 nerves or nerve-endings. 



The alkaloids were dissolved in filtered 

 plasma from the animal, or in sea water. Sea 

 water is isotonic with the blood (Dr. Garrey) 

 and is so slight a stimulant to the ganglion 

 as to be almost neutral. On the heart-muscle 

 I could not find that sea water had any efiect. 



The Effects of the Alkaloids on the Muscle. 

 — Atropin, curare, pilocarpin and physo- 

 stigmin of the strength of 1-100 in sea water 

 or plasma have apparently no effect on the 

 heart-muscle, the strength or the rate of the 

 heats not being altered. Digitalin and 

 nicotin of the same concentration produce 

 extreme tonus contraction when applied to the 

 ganglion-free segments. At a dikition of 

 1-1,000 digitalin applied to the muscle causes 

 increased strength of the contractions, fol- 

 lowed by a slight tonus. Nicotin produces 

 tonus contraction even at the dilution of 

 1-2,000. Veratrin at the dilution of 1-1,000 

 causes an initial diminution of the amplitude 

 of the beats, followed by strong tonus. At a 

 dilution of 1-100,000 or 1-500,000 the ampli- 

 tude of the beats is diminished, but no tonus 

 contraction is produced. Aconite was worked 

 with at a dilution of 1-100,000 and weaker ; at 

 that dilution it has apparently no effect on the 

 muscle. 



The Effects of the Alkaloids on the Ganglion 

 Cells. — Atropin, curare, pilocarpin and physo- 

 stig-min of the concentration of 1-100 (a 

 strength which has practically no effect on the 

 muscle) stimulate the ganglion cells intensely, 

 the beats becoming very rapid and in some 

 cases reduced to a minimum. The stimulat- 

 ing action of these drugs is best shown at a 

 dilution of 1-500 or 1-1,000; at this concen- 

 tration their effect on the nerve-cord is in the 

 direction of augmenting the rate and the 

 intensity of the nervous discharge from the 

 ganglion cells, that is, the rate and amplitude 

 of the beats in the ganglion-free reacting 

 portion of the heart are augmented. The 

 latent-time of the action of these drugs is very 



short, or from one half to five seconds, the 

 shorter, the stronger the solution and the more 

 excitable the nerve-cord. 



Nicotin, digitalin, veratrin and aconite at 

 the concentration of 1-100 stop the activity 

 of the ganglion cells instantaneously. That 

 this is a case of over stimulation or paralysis 

 and not a true depressor action is shown by 

 the fact that the stimulating action of these 

 allialoids is plainly evident on greater dilu- 

 tions. Veratrin is the most intense stimulant 

 of any of the alkaloids worked with. It miist 

 be diluted 1-1,000,000 or 1-2,000,000 in order 

 not to kill or paralyze the ganglion almost 

 instantaneously by over stimulation. At this 

 great dilution it still causes great augmenta- 

 tion of the rhythm of the ganglion cells. 

 Aconite stimulates the ganglion similarly at 

 the dilution of 1-100,000 or 1-500,000 ; nicotin 

 at the strength of 1-5,000 or 1-10,000; digi- 

 talin at the dilution of 1-1,000 or 1-2,000. 



The latent period of the stimulation is 

 short, or from one half to five seconds. At 

 the dilution of one to two millions veratrin 

 has often an initial depressor effect, which is 

 invariably followed by acceleration or stimula- 

 tion. Such an initial depressor action was 

 not observed in the case of any of the other 

 alkaloids. 



None of these alkaloids proves fatal to the 

 ganglion unless the application is long con- 

 tinued or their concentration great enough to 

 stop the activity of the ganglion cells at once, 

 and even in these cases the ganglion cells can 

 usually be brought back to almost normal 

 activity by continued bathing in plasma or 

 sea water. After a bath of ten seconds in 

 0.5 per cent, nicotin, 1 per cent, digitalin, or 

 1/500 per cent, veratrin I never succeeded in 

 restoring the ganglion. 



The action of these alkaloids is, therefore, 

 primarily on the ganglion cells in the heart 

 rather than on the nerve-fibers or the muscle- 

 cells. This is especially true of atropin, 

 curare, pilocarpin and physostigmin, as these 

 drugs have slight, if any, effect on the muscle 

 and motor nerve-endings at the concentration 

 of 1-100^ And it is also true of the other 

 alliialoids, or nicotin, digitalin, aconite and 

 veratrin, for although these drugs act strongly 



